Dietary Manipulation Research Articles

Increased dietary 5-hydroxytryptophan reduces fearfulness in red junglefowl hens (Gallus gallus).

Our production animals typically suffer poor welfare, which can be revealed by measuring the affective state these animals are in. Negative affective state is linked to poorer welfare, and can be measured as fearfulness. While continuing to research how to improve animal welfare, a compliment to reduce negative affective state could therefore be to reduce individuals' fearfulness, similar to how negative affective states are medicated in humans. A proposed mechanism for this is via the monoaminergic systems. This is based on previous studies across species that have linked the serotonergic system and fear-related behaviour. We here aimed to experimentally manipulate the serotonergic system in red junglefowl hens (Gallus gallus), the main ancestor of all domesticated chickens. We measured fearfulness as latency remaining immobile in a tonic immobility test, and did so both before and after our experimental manipulation. We set out to experimentally manipulate the serotonergic system via sub-chronic dietary treatment of 5-hydroxytryptophan (the precursor to serotonin). Our dietary manipulation of 5-hydroxytryptophan significantly reduced measured fearfulness in the manipulated hens, while latency in tonic immobility did not significantly change in our unmanipulated, control hens. This finding is promising since it indicates that increased tryptophan levels can be used to reduce fearfulness. Additionally, our result suggests that this can be done non-invasively via food (instead of injections), thus presenting a potentially feasible manipulation also for larger settings. Nevertheless, the serotonergic system is complex and its role in modulating behaviour in the fowl should be explored further to evaluate our findings, and more directly explored also in a production setting.

Development of pancreatic islet cells in the extrahepatic bile ducts of rats with experimentally-induced metabolic syndrome

Context There is data about the existence of some endocrine cells in the epithelial layer of the bile duct in humans and rats. Objective We evaluated Ghrelin-, Insulin-, Glucagon- and Somatostatin-positive cells in peribiliary glands, mast cells, and nerve fibres. Materials and methods Wistar rats were used for dietary manipulation with a 15% fructose solution for 12 weeks. Tissue samples were elaborated with immunohistochemistry for Insulin, Glucagon, Ghrelin, and Somatostatin. Glucose and lipid parameters were studied. Results In treated animals, Ghrelin+ and Insulin+ cells in perybiliary glands (PBGs) were significantly increased. In the male fructose group there was a significant increase of the homeostasis model assessment insulin resistance (HOMA-IR). Conclusions Stem/progenitor cells in extrahepatic bile tree (EHBT) could be a source of Insulin-producing cells in metabolic syndrome. Fructose treatment induces the increase of Ghrelin+ and Insulin+ cells in PBGs and the elevation of Insulin and Ghrelin plasma concentration.

Refining the study of decision-making in animals: differential effects of d-amphetamine and haloperidol in a novel touchscreen-automated Rearing-Effort Discounting (RED) task and the Fixed-Ratio Effort Discounting (FRED) task

Effort-based decision-making is impaired in multiple psychopathologies leading to significant impacts on the daily life of patients. Preclinical studies of this important transdiagnostic symptom in rodents are hampered, however, by limitations present in currently available decision-making tests, including the presence of delayed reinforcement and off-target cognitive demands. Such possible confounding factors can complicate the interpretation of results in terms of decision-making per se. In this study we addressed this problem using a novel touchscreen Rearing-Effort Discounting (RED) task in which mice choose between two single-touch responses: rearing up to touch an increasingly higher positioned stimulus to obtain a High Reward (HR) or touching a lower stimulus to obtain a Low Reward (LR). To explore the putative advantages of this new approach, RED was compared with a touchscreen version of the well-studied Fixed Ratio-based Effort Discounting (FRED) task, in which multiple touches are required to obtain an HR, and a single response is required to obtain an LR. Results from dopaminergic (haloperidol and d-amphetamine), behavioral (changes in the order of effort demand; fixed-ratio schedule in FRED or response height in RED), and dietary manipulations (reward devaluation by pre-feeding) were consistent with the presence of variables that may complicate interpretation of conventional decision-making tasks, and demonstrate how RED appears to minimize such variables.

The global anaerobic metabolism regulator fnr is necessary for the degradation of food dyes and drugs by Escherichia coli.

This work has broad relevance due to the ubiquity of dyes containing azo bonds in food and drugs. We report that azo dyes can be degraded by human gut bacteria through both enzymatic and nonenzymatic mechanisms, even from a single gut bacterial species. Furthermore, we revealed that environmental factors, oxygen, and L-Cysteine control the ability of E. coli to degrade azo dyes due to their impacts on bacterial transcription and metabolism. These results open up new opportunities to manipulate the azoreductase activity of the gut microbiome through the manipulation of host diet, suggest that azoreductase potential may be altered in patients suffering from gastrointestinal disease, and highlight the importance of studying bacterial enzymes for drug metabolism in their natural cellular and ecological context.

The Effects of Diet on the Immune Responses of the Oriental Armyworm Mythimna separata.

Nutrients can greatly affect host immune defenses against infection. Possessing a simple immune system, insects have been widely used as models to address the relationships between nutrition and immunity. The effects of high versus low protein-to-carbohydrate ratio (P:C) diets on insect immune responses vary in different studies. To reveal the dietary manipulation of immune responses in the polyphagous agricultural pest oriental armyworm, we examined immune gene expression, phenoloxidase (PO) activity, and phagocytosis to investigate the immune traits of bacteria-challenged oriental armyworms, which were fed different P:C ratio diets. We found the oriental armyworms that were fed a 35:7 (P:C) diet showed higher phenoloxidase (PO) activity and stronger melanization, and those reared on a 28:14 (P:C) diet showed higher antimicrobial activity. However, different P:C diets had no apparent effect on the hemocyte number and phagocytosis. These results overall indicate that high P:C diets differently optimize humoral immune defense responses in oriental armyworms, i.e., PO-mediated melanization and antimicrobial peptide synthesis in response to bacteria challenge.

Prolonged cyclical loading induces Haversian remodeling in mandibles of growing rabbits.

Bone adaptation to mechanical loading happens predominantly via modeling and remodeling, but the latter is poorly understood. Haversian remodeling (cortical bone replacement resulting in secondary osteons) is thought to occur in regions of low strain as part of bone maintenance or high strain in response to microdamage. However, analyses of remodeling in primates have revealed an unappreciated association with the number of daily load cycles. We tested this relationship by raising 30 male domestic rabbits (Oryctolagus cuniculus) on disparate diets from weaning to adulthood (48 weeks), facilitating a naturalistic perspective on mandibular bone adaptation. A control group consumed only rabbit pellets and an 'overuse' group ate hay in addition to pellets. To process hay, which is tougher and stiffer, rabbits increase chewing investment and duration without increasing bite force (i.e. corpus mean peak strain is similar for the two foods). Corpus remodeling in overuse rabbits was ∼1.5 times that of controls, measured as osteon population density and percentage Haversian bone. In the same subjects, there was a significant increase in overuse corpus bone formation (ratio of cortical area to cranial length), consistent with previous reports on the same dietary manipulation and bone formation in rabbits. This is the first evidence that both modeling and remodeling are simultaneously driven by the number of load cycles, independent of strain magnitude. This novel finding provides unique data on the feeding apparatus, challenges traditional thought on Haversian remodeling, and highlights the need for experimental studies of skeletal adaptation that examine mechanical factors beyond strain magnitude.

Dietary Interventions in Heart Failure with Preserved Ejection Fraction (HFpEF): a systematic scoping review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Evelyn Trust. Background Pharmacotherapies have improved outcomes for patients with Heart Failure with reduced Ejection Fraction (HFrEF), but less so for patients with HFpEF. Limited treatments results in substantial burden at personal, clinical and economic levels. Diet has been implicated in the pathogenesis and prognosis of HFpEF, as such, dietary manipulation has the potential to be a useful management strategy. Purpose The aim of the scoping review was to establish which nutritional interventions have so far been tested in patients with HFpEF and establish how the dietary manipulation was achieved. The aim of the meta-analysis was to quantify the effects of interventions tested to determine whether there is evidence to support specific dietary recommendations in patients with HFpEF. Methods Key word searches were performed in five bibliographic databases to identify randomised or controlled studies of dietary interventions conducted in HFpEF or mixed heart failure (HF) samples. Study characteristics were summarised according to PICO (population, intervention, comparator, outcome) categories and intervention complexity was assessed. Studies included in the meta-analysis were appraised for bias and the quality of the body of evidence was assessed via the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework. Results Twenty-five different interventions reported across 31 papers were identified. Only ten (40%) were conducted exclusively in HFpEF subjects. Studies employing highly tailored prescribed methods were most common (n=12, 48%). Dietary supplementation (n=10, 40%) and dietary pattern manipulations (n=3, 12%) were less represented. Seventeen studies were considered for meta-analysis; all but one were judged to be at high risk of bias. There was moderate quality evidence that caloric restriction led to clinically meaningful improvements in blood pressure and body weight. There was moderate quality evidence carbohydrate restriction resulted in meaningful reductions in blood pressure. There was very low quality evidence protein supplementation improved blood pressure and body weight and moderate quality evidence for clinically meaningful improvements in function. Conclusions Very few dietary interventions have been tested in HFpEF specifically. Most interventions tested were complex at the patient level, which may not be suitable for the older, multi-morbid patients who typify HFpEF. Results of meta-analyses performed were not of sufficient quality to make generalised conclusions. Some interventions delivered clinically meaningful changes that may be important to patients, therefore, clinicians could draw on these findings to inform personalised care plans and treatment goals.

P16-043-23 The Effects of Vigorous Intensity Exercise and Dietary Manipulation on Substrate Oxidation in the Postprandial Period

P16-043-23 The Effects of Vigorous Intensity Exercise and Dietary Manipulation on Substrate Oxidation in the Postprandial Period

A review on livestock odor characteristics and management (III) : Livestock odor control by dietary manipulation, in-housing management and manure management

A review on livestock odor characteristics and management (III) : Livestock odor control by dietary manipulation, in-housing management and manure management

Dietary Manipulation of Amino Acids for Cancer Therapy.

Cancer cells cannot proliferate and survive unless they obtain sufficient levels of the 20 proteinogenic amino acids (AAs). Unlike normal cells, cancer cells have genetic and metabolic alterations that may limit their capacity to obtain adequate levels of the 20 AAs in challenging metabolic environments. However, since normal diets provide all AAs at relatively constant levels and ratios, these potentially lethal genetic and metabolic defects are eventually harmless to cancer cells. If we temporarily replace the normal diet of cancer patients with artificial diets in which the levels of specific AAs are manipulated, cancer cells may be unable to proliferate and survive. This article reviews in vivo studies that have evaluated the antitumor activity of diets restricted in or supplemented with the 20 proteinogenic AAs, individually and in combination. It also reviews our recent studies that show that manipulating the levels of several AAs simultaneously can lead to marked survival improvements in mice with metastatic cancers.

Bioorthogonal Stimulated Raman Scattering Imaging Uncovers Lipid Metabolic Dynamics in Drosophila Brain During Aging.

Studies have shown that brain lipid metabolism is associated with biological aging and influenced by dietary and genetic manipulations; however, the underlying mechanisms are elusive. High-resolution imaging techniques propose a novel and potent approach to understanding lipid metabolic dynamics in situ. Applying deuterium water (D2O) probing with stimulated Raman scattering (DO-SRS) microscopy, we revealed that lipid metabolic activity in Drosophila brain decreased with aging in a sex-dependent manner. Female flies showed an earlier occurrence of lipid turnover decrease than males. Dietary restriction (DR) and downregulation of insulin/IGF-1 signaling (IIS) pathway, two scenarios for lifespan extension, led to significant enhancements of brain lipid turnover in old flies. Combining SRS imaging with deuterated bioorthogonal probes (deuterated glucose and deuterated acetate), we discovered that, under DR treatment and downregulation of IIS pathway, brain metabolism shifted to use acetate as a major carbon source for lipid synthesis. For the first time, our study directly visualizes and quantifies spatiotemporal alterations of lipid turnover in Drosophila brain at the single organelle (lipid droplet) level. Our study not only demonstrates a new approach for studying brain lipid metabolic activity in situ but also illuminates the interconnection of aging, dietary, and genetic manipulations on brain lipid metabolic regulation.

Birth weight and hypertension: nature or nurture?

Birth weight and hypertension: nature or nurture?

Associations between Plasma Lipid Mediators and Chronic Daily Headache Outcomes in Patients Randomized to a Low Linoleic Acid Diet with or without Added Omega-3 Fatty Acids.

A previous report showed that 12-week lowering of dietary omega-6 linoleic acid (LA) coupled with increased omega-3 polyunsaturated fatty acid (PUFA) intake (H3-L6 diet) reduced headache frequency and improved quality of life in patients with chronic daily headaches (CDHs) compared to dietary LA reduction alone (L6 diet). The trial also showed that targeted dietary manipulation alters PUFA-derived lipid mediators and endocannabinoids. However, several additional classes of lipid mediators associated with pain in preclinical models were not measured. The current secondary analysis investigated whether the clinical benefits of the H3-L6 diet were related to changes in plasma unesterified PUFA-derived lipid mediators known to be involved in nociception, including prostanoids. Lipid mediators were measured by ultra-high-pressure liquid chromatography coupled with tandem mass-spectrometry. Compared to baseline, dietary LA lowering with or without added omega-3 fatty acids did not alter unesterified n-6 PUFA-derived lipid mediators, although several species derived from LA, di-homo-gamma-linolenic acid, and arachidonic acid were positively associated with headache frequency and intensity, as well as mental health burden. Alpha-linolenic acid (ALA)-derived metabolites were also associated with increased headache frequency and intensity, although they did not change from the baseline in either dietary group. Compared to baseline, docosahexaenoic acid (DHA)-derived epoxides were more elevated in the H3-L6 group compared to the L6 group. Diet-induced elevations in plasma DHA-epoxides were associated with reduced headache frequency, better physical and mental health, and improved quality of life (p < 0.05). Prostanoids were not detected, except for PGF2-alpha, which was not associated with any outcomes. This study demonstrates that diet-induced changes in DHA-epoxides were associated with pain reduction in patients with chronic headaches, whereas n-6 PUFA and ALA metabolites were associated with nociception. Lipid mediator associations with mental health and quality of life paralleled pain management outcomes in this population. The findings point to a network of multiple diet-modifiable lipid mediator targets for pain management in individuals with CDHs.

Gut Immunobiosis and Biomodulators

The human gastrointestinal (GI) tract hosts complex and dynamic populations of microorganisms (gut microbiota) in advantageous symbiosis with the host organism through sophisticated molecular cross-talk. The balance and diversification within microbial communities (eubiosis) are crucial for the immune and metabolic homeostasis of the host, as well as for inhibiting pathogen penetration. In contrast, compositional dysregulation of the microbiota (dysbiosis) is blamed for the determinism of numerous diseases. Although further advances in the so-called ‘omics’ disciplines are needed, dietary manipulation of the gut microbial ecosystem through biomodulators (prebiotics, probiotics, symbionts, and postbiotics) represents an intriguing target to stabilize and/or restore eubiosis. Recently, new approaches have been developed for the production of infant formulas supplemented with prebiotics (human milk oligosaccharides [HMOs], galacto-oligosaccharides [GOS], fructo-oligosaccharides [FOS]), probiotics, and postbiotics to obtain formulas that are nutritionally and biologically equivalent to human milk (closer to the reference).

Macroalgae Improve the Growth and Physiological Health of White Shrimp (Litopenaeus vannamei)

This study compared and evaluated the effects of nine native macroalgae species on the tropic coast of China on the growth and physiological health performance of white shrimp (Litopenaeus vannamei). Nine hundred juvenile shrimps weighing 1.6 ± 0.02 g were fed with nine different types of macroalgae for 28 days. The experimental groups were as follows: Con (the diet without macroalgae), CRA (Caulerpa racemosa), CLA (Caulerpa lentillifera), CSS (Caulerpa sertularioides), CLM (Chaetomorpha linum), ULA (Ulva lactuca), GBE (Gracilaria bailiniae), ASA (Acanthophora spicifera), SVC (Sargassum ilicifolium var. conduplicatum), and BGE (Betaphycus gelatinae). Results showed that the growth performance of shrimps fed on the macroalgae meals was significantly higher than that of the control group ( P &lt; 0.05 ). The immune defense capacity (total hemocyte count, phagocytosis respiratory bursts, prophenoloxidase system, hemagglutination activity, and antibacterial and bacteriolytic activities) and antioxidant capacity (total antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde) of L. vannamei fed on macroalgae meals were significantly higher than those of the control group ( P &lt; 0.05 ). Specifically, the shrimps in the ASA group had the significantly higher physiological health level than shrimps in the other macroalgae groups ( P &lt; 0.05 ), and the expression of immune and antioxidation-related genes was also significantly higher in the ASA group ( P &lt; 0.05 ). Principal component analysis (PCA) demonstrated that optimal growth and physiological health efficacy were observed in the ASA group. In summary, this study suggested dietary manipulation using macroalgae to improve the growth performance, immune performance, and antioxidant capacity of L. vannamei, with the optimal macroalgae for the diet being Acanthophora spicifera.

Growth performance and cecal microbiota of broiler chicks as affected by drinking water disinfection and/or herbal extract blend supplementation

Environmental exposures during early life are important for animals' intestinal microbiota composition and their production performance. This experiment investigated the growth performance, hematology parameters, jejunal morphology, and cecal microbiota of broiler chicks as affected by exogenous factors from the aspects of drinking water quality and dietary manipulation. A total of 480-day-old broiler chicks (Arbor acre; 41.59 ± 0.88 g) were randomly assigned into 4 groups (CON, HWGM, CA, CAHWGM). Each group had 6 replicates with 20 birds per replicate. Broiler chicks in CON group were fed with basal diet and drank normal drinking water; in HWGM group were fed with basal diet supplemented with 1.5g/kg herbal extract blend (hops, grape seed, and wheat germ) and drank normal drinking water; in CA group were fed with basal diet and drank sodium dichlorocyanurate (50 mg/L) treated-drinking water; in CAHWGM group were fed with basal diet supplemented with 1.5 g/kg herbal extract blend and drank chlorinated drinking water. The experimental period was 42 d. We found that broiler chicks drank chlorinated drinking water led to an increase in body weight gain and feed efficiency during d 22 to 42 and 1 to 42, as well as a decrease in cecal Dysgonomonas and Providencia abundance. Dietary supplementation of herbal extract blend increased cecal Lactobacillus and Enterococcus abundance, whereas decreased Dysgonomonas abundance. Moreover, we observed that cecal Dysgonomonas abundance synergistically decreased by treating drinking water with sodium dichlorocyanurate and supplementing herbal extract blend to the diet. Therefore, results obtained in this study indicated that providing chlorinated drinking water is an effective strategy to improve the growth performance of broiler chicks by regulating intestinal microbiota. Additionally, dietary supplementation of herbal extract blend alone or combined with chlorinated drinking water is able to regulate cecal microbiota.

Role of peptide transporters in small peptide uptake of bovine mammary epithelial cells cultured in a transwell chamber.

Small peptides can be absorbed by the bovine mammary gland for the synthesis of milk protein, but the absorption mechanism still needs further study. In this study, the role of peptide transporters in small peptide uptake by bovine mammary epithelial cells (BMECs) was studied. First, BMECs were obtained and cultured in a transwell chamber. After 5 days of culture, the FITC-dextran permeability of the cell layer was detected. Then, 0.5 mM methionyl-methionine (Met-Met) was added to the medium of the lower and upper transwell chambers, respectively. The culture medium and BMECs were collected after 24 h of treatment. Liquid chromatography-mass spectrometry (LC-MS) was used to detect the concentration of Met-Met in the culture medium. Real-time PCR was used to detect the mRNA abundance of β-casein, oligopeptide transporter 2 (PepT2), and small peptide histidine transporter 1 (PhT1) in BMECs. Then, the BMECs were transfected with siRNA-PepT2 and siRNA-PhT1, respectively, and the uptake of β-Ala-Lys-N-7-amino-4-methylcoumarin-3-acetic acid (β-Ala-Lys-AMCA) in BMECs was detected. The results showed that, after 5 days of culture, the FITC-dextran permeability of BMECs was 0.6%, which was significantly lower than that of the control group. The absorption rates of Met-Met in the culture medium of the upper and lower chambers were 99.99% and 99.95%, respectively. The addition of Met-Met to the upper chamber significantly increased the mRNA abundance of β-casein and PepT2. The addition of Met-Met to the lower chamber significantly improved the mRNA abundance of β-casein, PepT2, and PhT1. The uptake of β-Ala-Lys-AMCA significantly decreased in BMECs transfected with siRNA-PepT2. These results suggested that the BMECs were successfully cultured in the transwell chamber and formed a cell layer with little permeability. The small peptides in both the upper and lower chambers of the transwell can be absorbed by BMECs in different ways. PepT2 plays an important role in the uptake of small peptides on both the basal and apical sides of BMECs, and PhT1 may be involved in the uptake of small peptides on the basal side of BMECs. Therefore, the addition of small peptides in dairy cow diets may be an effective dietary manipulation to increase milk protein concentration or yield.

Cardiac Hamp mRNA Is Predominantly Expressed in the Right Atrium and Does Not Respond to Iron

Hepcidin is a liver-derived hormone that controls systemic iron traffic. It is also expressed in the heart, where it acts locally. We utilized cell and mouse models to study the regulation, expression, and function of cardiac hepcidin. Hepcidin-encoding Hamp mRNA was induced upon differentiation of C2C12 cells to a cardiomyocyte-like phenotype and was not further stimulated by BMP6, BMP2, or IL-6, the major inducers of hepatic hepcidin. The mRNAs encoding hepcidin and its upstream regulator hemojuvelin (Hjv) are primarily expressed in the atria of the heart, with ~20-fold higher Hamp mRNA levels in the right vs. left atrium and negligible expression in the ventricles and apex. Hjv-/- mice, a model of hemochromatosis due to suppression of liver hepcidin, exhibit only modest cardiac Hamp deficiency and minor cardiac dysfunction. Dietary iron manipulations did not significantly affect cardiac Hamp mRNA in the atria of wild-type or Hjv-/- mice. Two weeks following myocardial infarction, Hamp was robustly induced in the liver and heart apex but not atria, possibly in response to inflammation. We conclude that cardiac Hamp is predominantly expressed in the right atrium and is partially regulated by Hjv; however, it does not respond to iron and other inducers of hepatic hepcidin.

Sex-biased gene expression in nutrient-sensing pathways.

Differences in lifespan between males and females are found across many taxa and may be determined, at least in part, by differential responses to diet. Here we tested the hypothesis that the higher dietary sensitivity of female lifespan is mediated by higher and more dynamic expression in nutrient-sensing pathways in females. We first reanalysed existing RNA-seq data, focusing on 17 nutrient-sensing genes with reported lifespan effects. This revealed, consistent with the hypothesis, a dominant pattern of female-biased gene expression, and among sex-biased genes there tended to be a loss of female-bias after mating. We then tested directly the expression of these 17 nutrient-sensing genes in wild-type third instar larvae, once-mated 5- and 16-day-old adults. This confirmed sex-biased gene expression and showed that it was generally absent in larvae, but frequent and stable in adults. Overall, the findings suggest a proximate explanation for the sensitivity of female lifespan to dietary manipulations. We suggest that the contrasting selective pressures to which males and females are subject create differing nutritional demands and requirements, resulting in sex differences in lifespan. This underscores the potential importance of the health impacts of sex-specific dietary responses.

The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline

Flavonoids are a biodiverse family of dietary compounds that have antioxidant, anti-inflammatory, antiviral, and antibacterial cell protective profiles. They have received considerable attention as potential therapeutic agents in biomedicine and have been widely used in traditional complimentary medicine for generations. Such complimentary medical herbal formulations are extremely complex mixtures of many pharmacologically active compounds that provide a therapeutic outcome through a network pharmacological effects of considerable complexity. Methods are emerging to determine the active components used in complimentary medicine and their therapeutic targets and to decipher the complexities of how network pharmacology provides such therapeutic effects. The gut microbiome has important roles to play in the generation of bioactive flavonoid metabolites retaining or exceeding the antioxidative and anti-inflammatory properties of the intact flavonoid and, in some cases, new antitumor and antineurodegenerative bioactivities. Certain food items have been identified with high prebiotic profiles suggesting that neutraceutical supplementation may be beneficially employed to preserve a healthy population of bacterial symbiont species and minimize the establishment of harmful pathogenic organisms. Gut health is an important consideration effecting the overall health and wellbeing of linked organ systems. Bioconversion of dietary flavonoid components in the gut generates therapeutic metabolites that can also be transported by the vagus nerve and systemic circulation to brain cell populations to exert a beneficial effect. This is particularly important in a number of neurological disorders (autism, bipolar disorder, AD, PD) characterized by effects on moods, resulting in depression and anxiety, impaired motor function, and long-term cognitive decline. Native flavonoids have many beneficial properties in the alleviation of inflammation in tissues, however, concerns have been raised that therapeutic levels of flavonoids may not be achieved, thus allowing them to display optimal therapeutic effects. Dietary manipulation and vagal stimulation have both yielded beneficial responses in the treatment of autism spectrum disorders, depression, and anxiety, establishing the vagal nerve as a route of communication in the gut-brain axis with established roles in disease intervention. While a number of native flavonoids are beneficial in the treatment of neurological disorders and are known to penetrate the blood-brain barrier, microbiome-generated flavonoid metabolites (e.g., protocatechuic acid, urolithins, γ-valerolactones), which retain the antioxidant and anti-inflammatory potency of the native flavonoid in addition to bioactive properties that promote mitochondrial health and cerebrovascular microcapillary function, should also be considered as potential biotherapeutic agents. Studies are warranted to experimentally examine the efficacy of flavonoid metabolites directly, as they emerge as novel therapeutic options.